Different agonist binding properties of M1 and M2 muscarinic receptors in calf brain cortex membranes.
Different agonist binding properties of M1 and M2 muscarinic receptors in calf brain cortex membranes.
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小牛大脑皮质膜中 M1 和 M2 毒蕈碱受体的不同激动剂结合特性。
DOI：
10.1016/0006-2952(87)90569-7
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发表时间：
1987
影响因子：
5.8
通讯作者：
G. Vauquelin
中科院分区：
文献类型：
--
作者：
P. Vanderheyden;G. Ebinger;G. Vauquelin
毒蕈碱拮抗剂1-[benzilic 4,4'-3H]-quinuclidinyl benzilate [3H]- qnb)结合在小牛大脑皮层膜上的一类非合作位点（KD= 0.29 nM, bmax = 1.06pM/mg蛋白）。计算机辅助分析浅皮伦齐平/[3H]-QNB竞争结合曲线表明，这些位点中68%为m1亚型，其余32%为M2亚型。吡仑西平的ki值分别为27 nM和1.14 μM。通过与0.5 nM [3H]-QNB在2 μM吡仑西平存在下的竞争结合，评价了拮抗剂阿托品和激动剂卡巴醇对M2的结合特性。M1受体的结合特性可以通过从总曲线中减去M2的曲线间接得到，也可以通过与0.3nM [3H]-匹伦齐平的竞争结合直接得到。M1和M2的阿托品竞争曲线较陡，且不受1 mM GTP和1 mM n -乙基酰亚胺的影响。对M2而言，草碱竞争曲线较浅。M1的陡峭曲线表明该受体亚类仅由低激动剂亲和力位点组成。GTP导致M2的碳酒精竞争曲线向右移动和变陡，但对M1的曲线没有影响。n -乙基马来酰亚胺引起了M2的碳醇竞争曲线的左移和变陡，并取消了GTP调制。M1也观察到左移，但幅度较小（即M1为3 - 4倍，而M2为17倍）。这些数据表明，在犊牛脑皮层，M1和M2受体对GTP和n -乙基马来酰亚胺调节表现出不同的敏感性。
The muscarinic antagonist 1-[benzilic 4,4'-3H]-quinuclidinyl benzilate [3H]-QNB) bound to a single class of non-cooperative sites in calf cerebral cortex membranes (KD= 0.29 nM andBmax= 1.06pM/mg protein). Computer-assisted analysis of the shallow pirenzepine/[3H]-QNB competition binding curves indicated that 68% of these sites were of the M1-subtype and the remaining 32% of the M2 subtype. RespectiveKi-values for pirenzepine were 27 nM and 1.14 μM. Binding characteristics of the antagonist atropine and of the agonist carbachol for M2 were evaluated by performing competition binding with 0.5 nM [3H]-QNB in the presence of 2 μM pirenzepine. The binding characteristics for the M1 receptors were obtained indirectly by subtracting the curve for M2 from the total curve, or directly by competition binding with 0.3nM [3H]-pirenzepine. Atropine competition curves were steep for M1 and M2 and were not affected by 1 mM GTP nor by 1 mM N-ethylmaleimide. The carbachol competition curve was shallow for M2. The steep curves for M1 indicate that this receptor subclass was only composed of low agonist affinity sites. GTP, which caused a rightward shift and a steepening of the carbachol competition curve for M2, did not affect the curves for M1.N-ethylmaleimide provoked a leftward shift and a steepening of the carbachol competition curve for M2 and abolished GTP modulation. A leftward shift was also observed for M1, but of a smaller magnitude (i.e. 3–4-fold for M1 compared to 17-fold for M2). These data suggest that, in calf brain cortex, M1 and M2 receptors show different susceptibility towards GTP andN-ethylmaleimide modulation.
大鼠中[3H]哌仑西平结合的独特调节特征和区域分布为不同的 M1 和 M2 毒蕈碱受体亚型提供了证据。
影响因子：
6.1
作者：
Watson,M;Yamamura,HI;Roeske,WR
通讯作者：
Roeske,WR